1. Field of the Invention
The present invention relates generally to the fields of biomedical engineering, medicine and imaging. More particularly, it concerns a new process to increase light transmission in biological media by using either index matching agents to reduce the amount of random reflection and refraction in tissue which, in turn, reduces light scattering or agents that reduce absorption and allow improved tissue imaging and delivery of light into tissues for diagnoses and treatment.
2. Description of Related Art
Many biological media or tissues, such as human skin, are optically turbid and highly light scattering because of the refractive index (n) variations among water and various inter/intra cellular components. The refractive index of water is 1.33 while many cellular components have higher refractive indices. For instance, melanin has a refractive index of 1.7 (Vitkin et al., 1994), nucleus has a refractive index of 1.36 Hiramoto, 1979) and dehydrated collagen has a refactive index of 1.53 (Wang et al., 1996). Reflection and refraction occur when light travels from a medium with one refractive index to another medium having a different index. Greater index mis-match generally increases the amount of light reflection and refraction As a result, light scatters randomly inside tissues mainly due to the index mis-match between cellular/subcellular water and the spatial distribution of various cellular components.
Imaging through tissue is always degraded by the strong optical scattering in biological tissue and any imaging technique must either discriminate in favor of the unscattered "ballistic" light signal (which is usually extremely weak) or must take account of the multiple scattering in some image reconstruction algorithm based on inverse scattering. Both approaches limit the visualization of the underlying tissue and in many cases turbid tissues cannot be sufficiently distinguished from each other. Thus many optical diagnostic and therapeutic techniques have limited capabilities.
Many current medical monitoring techniques require puncturing the skin to draw blood. For example, diabetics must measure the glucose concentration in blood samples which is extremely inconvenient and invasive, especially when one has to perform this task up to twenty times per day. A non-invasive blood glucose monitoring method is a goal of intensive research worldwide. One method uses the blood spectral absorbance to quantitatively determine glucose level, but the small glucose optical signature relative to noise and filtering associated with scattered light remains a serious constraint which has prevented the widespread adoption of this method for monitoring. Non-invasive devices are being developed to perform this absorbance measurement, but the signal to noise limitation must be reduced in order for these devices to be successful.
Development of noninvasive techniques appear to be further advanced for the visualization of the eye sclera, especially for the detection of cancers and cataracts. But these techniques have not been successfully applied to other tissues.
There are techniques which temporarily alter tissue optical properties such as stretching, coagulation and dehydration which cause the packing of cellular components to reduce reflection/refraction due to the cellular-water interface. Color dyes have been used to enhance local light absorption (DeCoste et al., 1992). Each of these techniques has limited applicability to living animals.
Radiation dispersing agents, irradiation and fluorescence have been used in combination to visualize and photosensitive tumor cells (U.S. Pat. No. 4,612,938). But this technique is designed to enhance visualization of tumor cells on the interior surface of hollow organ cavities instead of improving visualization of subsurface, non-oncogenic turbid tissues. Moderate mechanical compression has been used to increase local cellular concentration to enhance light absorption and reduce light scattering in order to improve the contrast between bone/teeth structure and skin (U.S. Pat. No. 5,429,120); however, this technique has very limited ability to improve the visualization of soft or turbid tissues and their structure.
None of these techniques provide the desired visualization of tissues which are normally turbid for diagnosis and treatment. Alternative techniques are needed to improve visualization for the diagnosis and monitoring of a variety of injuries and diseases and to enhance certain laser treatments and therapies. In addition, imaging modalities, such as optical coherence tomography (OCT) and confocal imaging, that are used for the diagnosis of pathological sites would benefit from an increased imaging distance.